Title |
A distinct innate lymphoid cell population regulates tumor-associated T cells
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Published in |
Nature Medicine, February 2017
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DOI | 10.1038/nm.4278 |
Pubmed ID | |
Authors |
Sarah Q Crome, Linh T Nguyen, Sandra Lopez-Verges, S Y Cindy Yang, Bernard Martin, Jennifer Y Yam, Dylan J Johnson, Jessica Nie, Michael Pniak, Pei Hua Yen, Anca Milea, Ramlogan Sowamber, Sarah Rachel Katz, Marcus Q Bernardini, Blaise A Clarke, Patricia A Shaw, Philipp A Lang, Hal K Berman, Trevor J Pugh, Lewis L Lanier, Pamela S Ohashi |
Abstract |
Antitumor T cells are subject to multiple mechanisms of negative regulation. Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor-infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56(+)CD3(-) population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56(+)CD3(-) cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells. |
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Geographical breakdown
Country | Count | As % |
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United States | 17 | 27% |
Canada | 7 | 11% |
Panama | 3 | 5% |
United Kingdom | 3 | 5% |
Mexico | 2 | 3% |
Korea, Republic of | 1 | 2% |
Norway | 1 | 2% |
Trinidad and Tobago | 1 | 2% |
Denmark | 1 | 2% |
Other | 5 | 8% |
Unknown | 23 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 33 | 52% |
Scientists | 18 | 28% |
Practitioners (doctors, other healthcare professionals) | 8 | 13% |
Science communicators (journalists, bloggers, editors) | 5 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 2 | <1% |
France | 1 | <1% |
Unknown | 327 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 93 | 28% |
Student > Ph. D. Student | 73 | 22% |
Student > Master | 34 | 10% |
Student > Doctoral Student | 17 | 5% |
Student > Bachelor | 15 | 5% |
Other | 52 | 16% |
Unknown | 46 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 96 | 29% |
Agricultural and Biological Sciences | 70 | 21% |
Biochemistry, Genetics and Molecular Biology | 47 | 14% |
Medicine and Dentistry | 41 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 2% |
Other | 16 | 5% |
Unknown | 52 | 16% |